Disease or injury often requires amputation of a portion of a limb. If the remaining bone is too short for prosthesis attachment, the patient has serious problems with the functions dependent on the missing portion of the patient's body. Often this harms lifestyle and causes deterioration of bodily functions that diminish longevity and have undesirable emotional and mental health consequences. Especially difficult are injuries to military personnel caused by improvised explosive devices. There is an urgent need for surgical devices and methods to help these severely disabled amputees.
Every patient has a unique situation. If the remaining portion of the limb can be elongated and provided with a functional structure for prosthesis attachment, the patient's prospects will be greatly improved. There is an urgent need for a device and method to elongate bone and to provide for prosthesis attachment.
Liver and bone are the only two organs of the human body that can regenerate after a loss of a part of the organ. Bone only regenerates when the loss is small, as in a simple fracture. About ten weeks is required to regain complete strength. For a larger defect from trauma or surgery, the surgeon may make the judgment that the bone will not regenerate even if it is held immobile in the proper position. In a fracture situation bone regenerates from both the proximal and distal bone fragments. A typical non-union results in closing at both ends with a somewhat hemispherical shape, with no bone in the gap between the fragments. This is true because the bone starts to regenerate from both ends of the defect until it rounds off with a hemispherical end before closing the gap, and no further regeneration will take place thereafter. When this is expected the surgeon must use a bone graft taken from the patient (autograft) or from the same species (allograft), usually a cadaver. These repairs take longer to heal and harvesting the bone for an autograft is a secondary surgery which is painful and increases the risk of infection and weakness at the harvest site. Because regeneration starts at both ends of the bone and because there is a limit at both ends for regenerating bone to grow, amputated bone has never been elongated. The bone end becomes rounded but elongation heretofore has not been possible.
The bone regeneration process is very complex and many factors affect regeneration with or without attempting to elongate it. An autograft is impractical when the harvested bone creates a similar defect, so some kind of artificial bone is needed. The challenge for elongating bone is to induce new bone to form at the distal end of the elongation so it can be a source of regeneration of connecting bone from both the proximal and distal ends and to prevent rounding off. The natural repair of a small loss of bone starts with a massive hematoma from capillaries and larger blood vessels. This produces a huge clot that quickly forms a fibrous scaffold when fibrinogen from the blood becomes a fibrous network. Once the network becomes strong, it is called a callus. For major injuries, several stages occur that take weeks or years to become dense, loading-bearing bone.
Stem cells for bone formation and for soft tissue formation appear from blood vessel walls and from pluripotent mesenchymal sources that are found in the waxy marrow of the long bones of the extremities, the sternum and the ilium. The delivery of the signals that stimulate the mesenchymal cells to produce the stem cells needed at a particular stage of regeneration is through systemic routes, such as the vascular system. The present state-of-the-art is based on harvesting a particular cell culture (only one of many that are needed), culturing it to multiply to high concentration, seeding a bone-like scaffold with high surface area and where further multiplication can take place, inoculating the scaffold/culture with growth factors, cytokines or bone morphogenic protein to increase multiplication rate, placing it surgically in a bone defect, and waiting for strong bone recovery. This method does not regenerate strong bone and has not been successful, but the description above shows how difficult it is. Note that the locations of mesenchymal cells are in places where they are protected from physical and chemical trauma and are surrounded by strong, protective bone.
Despite the worldwide efforts to make artificial bone, study stem cells, biomaterials, growth factors, antibiotics, etc. the basic sciences have not solved the problem of extension of amputated bone. Most of the efforts to make an artificial bone graft have depended on calcium phosphate and bioglasses as a tissue contact material or on tissue engineering to produce a graft that will be dissolved by tissue responses at the same rate as bone in rebuilding. Calcium phosphates and bioglasses, as possible bone graft substitutes, have been studied for over fifty years because they are not walled off by a foreign body response which invokes a fibrous capsule. All existing load-bearing materials used in current orthopedic practice are walled off, so the bone does not bond to them. The implants must be anchored in place by mechanical or geometric means, such as screws, beaded surfaces and cements (only PMMA cement is used for load-bearing applications. It has such undesirable tissue contact problems that it is used only if there is no other alternative.) Calcium phosphates and bioglasses are classical brittle materials that fail in tension when a local tensile stress at a flaw exceeds the fracture stress. Their bioactivity causes flaws to appear at tensile load locations making them completely unsuitable for load-bearing bone graft applications.
Tissue engineering has been studied for more than thirty years without achieving a successful load-bearing bone graft. The concept is based on three components: 1) cultured cells, such as a patient's osteoblasts, 2) a high surface area calcium phosphate scaffold on which the osteoblasts will grow in vitro and 3) growth factors to enhance the kinetics of cell growth and bone formation. The expectation that load-bearing bone will form on porous, weak, brittle, calcium phosphate scaffolds at the same rate the scaffolds are being resorbed is unjustified. The theory neglects the reality that the scaffold is too weak to support load even after bone is formed throughout because it will be disorganized chondroidal bone with very little strength. It also ignores the reality that the rate and character of bone formation depend on many factors, including applied load and the rate of scaffold resorption within the scaffold relative to the rate of scaffold resorption at the load-bearing bone/dense-bone interface. It would be very difficult for the rate of absorption to be adjusted to the rate of formation. What is needed is a permanent, bioactive strong, load-bearing implant.
The concept of a ceramic/ceramic composite was disclosed by McGee in U.S. Pat. No. 3,787,900. The first mineral in this composite is tricalcium phosphate which helps control tissue response and to prevent formation of a foreign body capsule. The second mineral in this composite is magnesium aluminate spinel, an inert biocompatible ceramic that gives the implant enduring strength. OSTEOCERAMIC is a brand of biologically active load bearing materials such as the one disclosed in McGee's U.S. Pat. No. 3,787,900.
The artificial OSTEOCERAMIC bone technology was modified in three later patents by McGee (U.S. Pat. Nos. 6,312,467, 6,364,909, and 6,719,793), through improved processing and sintering so that the external geometry could be utilized to guide bone generation and to which bone will bond. The implant became a “smart” implant (a “smart” material is one that repairs itself). The implant releases tricalcium phosphate at the crack surface and the local loss of strength induces adjacent bone to repair the implant/bone assembly to allow it to remain functional. The biologically active load bearing implant disclosed in U.S. Pat. No. 6,312,467 is the only load-bearing implant experimentally demonstrated to serve as a load-bearing artificial bone graft with only bone bonding to it to keep it functional.
A biologically active cement material was disclosed by McGee and Roemhildt in U.S. Pat. No. 6,723,334. This cement contains tricalcium phosphate to control tissue response and calcium aluminate as a hydraulic cement to cause the cement to set during surgery and to provide enduring strength. It is also a ceramic/ceramic composite sold under the OSTEOCERAMIC brand and is a smart material to which bone will bond.
Wolff's law states that bone remodels to support dynamic loads. The structure and strength of bone responds to loads. Skeletal loads are dynamic and experiments have shown that the remodeling to support load is faster and stronger if the load is dynamic. The dynamic load can be provided through physical therapy. When there is no load, regeneration produces weak non-load-bearing bone. Direct, load-bearing bone is only formed when the new bone has dynamic loading.
When a fracture occurs and bone is displaced it is necessary to reduce the fracture by realigning the displaced bone to its proper position and holding it in place until the bone regenerates. If the device holding it in place is insufficient, too much movement will occur and the newly forming repair bone will be destroyed. That movement is identified as macromotion and the amount of movement is called macrostrain. When the implants are put in place they must be held firmly enough in the correct position to avoid macromotion and the devices stabilizing them must be strong and rigid enough to prevent macromotion and macrostrain. For severe fractures the methods of holding them in place are usually internal and may include fastening a metal plate to the proximal and distal bone with the fracture reduced using bone screws as fasteners. Other means for securing such fractures is to use external fixation, where screws or wires are placed in the proximal and distal bone and an external cage is built around the limb so that the screws or wires hold the bones in their proper position. This requires a static (unchanging) load to be applied to the bone by the fixation devices.